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Series GSE39911 Query DataSets for GSE39911
Status Public on Aug 17, 2012
Title Transcriptome-wide Regulation of Splicing and mRNA Localization by Muscleblind Proteins
Organisms Drosophila melanogaster; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The Muscleblind-like (Mbnl) family of RNA-binding proteins plays important roles in muscle and eye development and in Myotonic Dystrophy (DM), where expanded CUG or CCUG repeats functionally deplete Mbnl proteins. We identified transcriptome-wide functional and biophysical targets of Mbnl proteins in brain, heart, muscle, and myoblasts using RNA sequencing and crosslinking/immunoprecipitation-sequencing approaches. This analysis identified several hundred splicing events whose regulation depended on Mbnl function, in a pattern indicative of functional interchangeability between Mbnl1 and Mbnl2. A nucleotide resolution RNA map associated repression or activation of exon splicing with Mbnl binding near either 3' splice site or near the downstream 5' splice site, respectively. Transcriptomic analysis of sub-cellular compartments uncovered a global role for Mbnls in regulating localization of mRNAs encoding membrane, synaptic and other proteins in both mouse and Drosophila cells, and Mbnls also contribute to protein secretion. These findings hold several new implications for DM pathogenesis.
Overall design To assess global functions of Muscleblind proteins, RNA-Seq was performed using WT and Mbnl1 KO brain, heart, and muscle (5 mice each). Additionally, C2C12 mouse myoblasts were depleted of Mbnl1, Mbnl2, or both. Subcellular fractionation experiments were performed to analyze mRNA localization following depletion of Mbnl1 and Mbnl2 in C2C12 mouse myoblasts, and following depletion of Mbnl in Drosophila S-2R+ cells. CLIP-Seq was also performed against Mbnl1 in mouse brain, heart, muscle, and C2C12 myoblasts. Finally, ribosome footprinting was performed with C2C12 mouse myoblasts that were depleted of Mbnl1, Mbnl2, or both.
Contributor(s) Wang ET, Cody NA, Jog S, Biancolella M, Wang TT, Treacy DJ, Luo S, Schroth GP, Housman DE, Reddy S, Lécuyer E, Burge CB
Citation(s) 22901804
Submission date Aug 06, 2012
Last update date May 15, 2019
Contact name Eric T Wang
Organization name University of Florida
Street address 2033 Mowry Rd
City Gainesville
State/province FL
ZIP/Postal code 32610
Country USA
Platforms (4)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (55)
GSM981180 brainKOa
GSM981181 brainKOb
GSM981182 brainKOc
BioProject PRJNA172014
SRA SRP014709

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Supplementary file Size Download File type/resource
GSE39911_RAW.tar 590.0 Kb (http)(custom) TAR (of BED)
GSE39911_fly_fractionation_RPKM.txt.gz 246.7 Kb (ftp)(http) TXT
GSE39911_myoblast_RPKM.txt.gz 444.3 Kb (ftp)(http) TXT
GSE39911_myoblast_fractionation_RPKM.txt.gz 480.6 Kb (ftp)(http) TXT
GSE39911_myoblast_ribo_RPKM.txt.gz 435.8 Kb (ftp)(http) TXT
GSE39911_tissue_RPKM.txt.gz 1.2 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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